Effect of the Melanocortin 4-Receptor Ile269Asn Mutation on Weight Loss Response to Dietary, Phentermine and Bariatric Surgery Interventions
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Populations
2.1.1. Case and Control Association
2.1.2. Dietary Intervention
2.1.3. Phentermine Intervention
2.1.4. Bariatric Surgery
2.1.5. Ile269Asn Carrier and Non-Carrier Matching in the Three Weight-Loss Intervention Groups
2.2. Anthropometric Measurements
2.3. Biochemical Measurements
2.4. MC4R Ile269Asn Genotyping
2.5. Local Ancestry Inference
2.6. Statistical Analysis
3. Results
3.1. Case–Control Association Study
3.2. Response to Dietary Intervention
3.3. Response to Phentermine Treatment after Six Months
3.4. Response to RYGB Surgery
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Stratified on BMI Level | n | Genotype n (%) | OR (95% CI) | p-Value | |
---|---|---|---|---|---|
Ile269Ile | Ile269Asn/Asn269Asn | ||||
Normal weight | 483 | 478 (99.0) | 5/0 (1.0) | ||
OB I–III | 1200 | 1154 (96.2) | 45/1 (3.8) | 3.8 (1.5–9.6) | 0.005 |
OB I/II | 942 | 910 (96.6) | 32/0 (3.4) | 3.4 (1.3–8.7) | 0.012 |
OB III | 258 | 244 (94.6) | 13/1 (5.4) | 5.5 (1.9–15.4) | 0.001 |
Ile269Asn MC4R Patient 1 | Ile269Asn MC4R Patient 2 | Control Group n = 6 | |||||||
---|---|---|---|---|---|---|---|---|---|
Baseline | 1 Month | ∆ | Baseline | 1 Month | ∆ | Baseline | 1 Month | ∆ | |
Weight (kg) | 133.6 | 129.6 | −4.0 | 116.6 | 114.8 | −1.8 | 105.5 ± 2.4 | 102.5 ± 2.8 | −2.9 ± 0.6 |
BMI (kg/m2) | 45.2 | 44.1 | −1.1 | 46.4 | 45.7 | −0.7 | 44.9 ± 1.0 | 43.6 ± 1.1 | −1.3 ± 0.2 |
Fat mass % | 46.8 | 46.4 | 0.5 | 55.9 | 54.9 | −1.0 | 53.5 ± 0.3 | 53.1 ± 0.4 | −0.4 ± 0.2 |
Skeletal muscle mass % | 30.0 | 30.4 | 0.5 | 24.5 | 25.0 | 0.5 | 25.8 ± 0.2 | 26.0 ± 0.2 | 0.2 ± 0.1 |
SBP (mmHg) | 110 | 123 | 13 | 110 | 93 | −17 | 111.6 ± 4.6 | 104.8 ± 4.7 | −6.8 ± 4.8 |
DBP (mmHg) | 80 | 86 | 6 | 75 | 66 | −9 | 79.3 ± 3.2 | 73.5 ± 4.1 | −5.8 ± 3.7 |
Glucose (mg/dL) | 99.5 | 105.3 | 5.88 | 139.6 | 117.9 | −21.7 | 105.2 ± 4.0 | 97.6 ± 2.4 | −7.6 ± 4.8 |
Insulin (μU/mL) | 16.9 | 20.8 | 3.87 | 30.7 | 32.9 | 2.18 | 25.2 ± 4.4 | 20.7 ± 3.3 | −4.5 ± 6.1 |
HOMA-IR | 4.16 | 5.4 | 1.25 | 10.6 | 9.6 | −1.0 | 6.5 ± 1.1 | 4.9 ± 0.8 | −1.5 ± 1.4 |
Adiponectin (μg/mL) | 5.67 | 6.3 | 0.59 | 9.7 | 11.7 | 2.0 | 8.2 ± 1.8 | 7.6 ± 1.3 | −0.6 ± 0.6 |
Leptin (ng/mL) | 71.4 | 52.9 | −18.5 | 98.7 | 92.5 | −6.2 | 67.8 ± 6.2 | 57.3 ± 5.5 | −10.5 ± 4.4 |
Ile269Asn MC4R n = 6 | Control Group n = 18 | Difference between Groups | ||||||||
---|---|---|---|---|---|---|---|---|---|---|
Baseline | 6 Months | ∆ | p-Value | Baseline | 6 Months | ∆ | p-Value | Mean Difference | p-Value | |
Weight (kg) | 83.7 ± 4.3 | 70.9 ± 4.8 | −12.7 ± 2.3 | 0.003 | 84.3 ± 1.6 | 72.9 ± 1.8 | −11.3 ± 0.9 | <0.001 | −1.4 ± 2.1 | 0.523 |
BMI (kg/m2) | 34.4 ± 1.3 | 29.2 ± 1.7 | −5.2 ± 0.9 | 0.003 | 34.2 ± 0.4 | 29.6 ± 0.6 | −4.5 ± 0.3 | <0.001 | −0.6 ± 0.8 | 0.447 |
% Fat mass | 48.2 ± 2.4 | 43.6 ± 2.4 | −4.6 ± 2.2 | 0.088 | 50.2 ± 0.6 | 45.4 ± 0.9 | −4.8 ± 0.5 | <0.001 | 0.1 ± 1.5 | 0.925 |
% Muscle mass | 22.8 ± 1.3 | 24.0 ± 4.0 | 1.2 ± 0.9 | 0.242 | 21.5 ± 0.3 | 23.1 ± 0.4 | 1.5 ± 0.2 | <0.001 | −0.3 ± 0.6 | 0.630 |
SBP (mmHg) | 105.0 ± 3.4 | 106.6 ± 2.4 | 2.0 ± 2.0 | 0.374 | 108.8 ± 2.2 | 103.3 ± 1.6 | −5.5 ± 2.2 | 0.027 | 7.5 ± 4.3 | 0.100 |
DBP (mmHg) | 75.0 ± 3.4 | 76.0 ± 2.4 | 2.0 ± 3.7 | 0.587 | 81.7 ± 5.4 | 72.2 ± 2.0 | −9.5 ± 6.1 | 0.097 | 11.5 ± 12 | 0.264 |
Glucose (mg/dL) | 97.3 ± 4.5 | 88.0 ± 3.5 | −9.3 ± 4.9 | 0.129 | 94.2 ± 1.9 | 84.0 ± 1.7 | −9.8 ± 2.4 | 0.001 | 0.4 ± 4.9 | 0.861 |
Insulin (μU/mL) | 13.0 ± 2.9 | 8.2 ± 1.5 | −4.8 ± 2.1 | 0.212 | 16.5 ± 2.2 | 8.3 ± 0.8 | −8.4 ± 2.6 | 0.001 | 3.6 ± 4.4 | 0.328 |
HOMA-IR | 3.2 ± 0.8 | 1.8 ± 0.3 | −1.4 ± 0.6 | 0.179 | 3.9 ± 0.6 | 1.7 ± 0.1 | −2.2 ± 0.7 | <0.001 | 0.8 ± 1.2 | 0.365 |
Adiponectin (μg/mL) | 3.7 ± 0.6 | 4.8 ± 0.7 | 1.1 ± 0.4 | 0.033 | 4.2 ± 0.4 | 7.0 ± 1.2 | 2.5 ± 1.2 | 0.062 | −1.4 ± 2.0 | 0.900 |
Leptin (ng/mL) | 24.7 ± 6.9 | 11.6 ± 3.4 | −13.1 ± 7.5 | 0.067 | 20.2 ± 1.8 | 15.2 ± 3.3 | −4.7 ± 4.1 | 0.039 | −8.3 ± 8.0 | 0.484 |
Parameter | Time | Ile269Asn MC4R | Control Group | p-Value |
---|---|---|---|---|
n = 7 | n = 24 | |||
Age (years) | Basal | 40.5 ± 2.9 | 40.9 ± 1.1 | 0.94 |
Weight (kg) | Basal | 111.5 ± 3.6 | 110.9 ± 3.5 | 0.70 |
6 months after RYGB | 76.9 ± 4.7 | 79.4 ± 2.9 | 0.62 | |
BMI (kg/m2) | Basal | 43.8 ± 1.6 | 42.5 ± 1.3 | 0.70 |
6 months after RYGB | 30.0 ± 1.8 | 30.7 ± 0.9 | 0.48 | |
%Hb1Ac | Basal | 5.8 ± 0.3 | 5.7 ± 0.1 | 0.48 |
6 months after RYGB | 5.4 ± 1.2 | 5.3 ± 0.1 | 0.39 | |
%WL | 6 months after RYGB | 29.9 ± 0.01 | 27.8 ± 0.01 | 0.73 |
%EWL | 6 months after RYGB | 66.6 ± 5.6 | 64.9 ± 3.1 | 0.51 |
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Salazar-Valencia, I.G.; Villamil-Ramírez, H.; Barajas-Olmos, F.; Guevara-Cruz, M.; Macias-Kauffer, L.R.; García-Ortiz, H.; Hernández-Vergara, O.; Díaz de Sandy-Galán, D.A.; León-Mimila, P.; Centeno-Cruz, F.; et al. Effect of the Melanocortin 4-Receptor Ile269Asn Mutation on Weight Loss Response to Dietary, Phentermine and Bariatric Surgery Interventions. Genes 2022, 13, 2267. https://doi.org/10.3390/genes13122267
Salazar-Valencia IG, Villamil-Ramírez H, Barajas-Olmos F, Guevara-Cruz M, Macias-Kauffer LR, García-Ortiz H, Hernández-Vergara O, Díaz de Sandy-Galán DA, León-Mimila P, Centeno-Cruz F, et al. Effect of the Melanocortin 4-Receptor Ile269Asn Mutation on Weight Loss Response to Dietary, Phentermine and Bariatric Surgery Interventions. Genes. 2022; 13(12):2267. https://doi.org/10.3390/genes13122267
Chicago/Turabian StyleSalazar-Valencia, Itzel G., Hugo Villamil-Ramírez, Francisco Barajas-Olmos, Martha Guevara-Cruz, Luis R. Macias-Kauffer, Humberto García-Ortiz, Omar Hernández-Vergara, David Alberto Díaz de Sandy-Galán, Paola León-Mimila, Federico Centeno-Cruz, and et al. 2022. "Effect of the Melanocortin 4-Receptor Ile269Asn Mutation on Weight Loss Response to Dietary, Phentermine and Bariatric Surgery Interventions" Genes 13, no. 12: 2267. https://doi.org/10.3390/genes13122267
APA StyleSalazar-Valencia, I. G., Villamil-Ramírez, H., Barajas-Olmos, F., Guevara-Cruz, M., Macias-Kauffer, L. R., García-Ortiz, H., Hernández-Vergara, O., Díaz de Sandy-Galán, D. A., León-Mimila, P., Centeno-Cruz, F., González-Salazar, L. E., Guizar-Heredia, R., Pichardo-Ontiveros, E., Jacobo-Albavera, L., Posadas-Sánchez, R., Vargas-Alarcón, G., Velazquez-Cruz, R., Gutiérrez-Aguilar, R., Zerrweck, C., ... Canizales-Quinteros, S. (2022). Effect of the Melanocortin 4-Receptor Ile269Asn Mutation on Weight Loss Response to Dietary, Phentermine and Bariatric Surgery Interventions. Genes, 13(12), 2267. https://doi.org/10.3390/genes13122267